A previously undescribed inflammatory myopathy (myositis) has recently been characterized in five related Dutch Shepherd dogs. Clinical signs include muscle tremors, pelvic limb stiffness, progressive weakness, and severe muscle atrophy. The age of onset was 3 – 9 months, and all were euthanized prior to 2 years of age due to painful muscular degeneration. Serum creatine kinase activity was elevated in all affected dogs. Histopathologic examination of muscle biopsies revealed multifocal areas of mixed mononuclear cell infiltration, myonecrosis and regeneration. Metabolomics data from these five cases gives functional support to mitochondrial involvement.
Research carried out at the University of Minnesota and the University of California, San Diego - Comparative Neuromuscular Laboratory indicates that this disease is inherited in an autosomal recessive manner. We have identified a mutation within a disease-associated mitochondrial transporter gene SLC25A12, and all affected dogs have two copies of this mutation. Population testing of 150 Dutch Shepherds indicates that the carrier rate of this mutation is currently ~8% (this represents a biased sample population, it may change as more dogs are tested).
Scientific References
A Mutation in the Mitochondrial Aspartate/Glutamate Carrier Leads to Intramitochondrial Oxidation and an Inflammatory Myopathy in Dutch Shepherd Dogs.
Diane Shelton, Minor KM, Li K, Naviaux JC, Monk J, Wang L, Guzik E2, Guo LT, Porcelli V, Gorgoglione R, Lasorsa M, Leegwater PJ, Persico AM, Mickelson JR, Palmieri L, Naviaux RK.
Journal of Neuromuscular Diseases 6 (2019) 485–501 doi: 10.3233/JND-190421.